Summary
The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 μg/kg) occurred 4 h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24 h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.
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Akera, T., Brody, T. M.: The addiction cycle to narcotics in the rat and its relation to catecholamines. Biochem. Pharmacol. 17, 675–688 (1968)
Ary, M., Cox, B., Lomax, P.: Dopaminergic mechanisms in precipitated withdrawal in morphine-dependent rats. J. Pharmacol. Exp. Ther. 200, 271–276 (1977)
Bieger, D., Larochelle, L., Hornykiewicz, O.: A model for the quantitative study of central dopaminergic and serotoninergic activity. Eur. J. Pharmacol. 18, 128–136 (1972)
Blasig, J., Meyer, G., Stádele, M.: Factors influencing the manifestation of dependence in rats. In: “Factors affecting the action of narcotics” (M. L. Adler, L. Manara, R. Samanin, eds.), pp. 133–146. New York: Raven Press 1978
Buckett, W. R.: A new test for morphine-like physical dependence (addiction liability) in rats. Psychopharmacologia (Berl.) 6, 410–416 (1964)
Cheney, D. L., Goldstein, A.: The effect of p-chlorophenylalanine on opiate-induced running, analgesia, tolerance and physical dependence in mice. J. Pharmacol. Exp. Ther. 177, 309–315 (1971)
Cicero, T. J., Meyer, E. R.: Morphine pellet implantation in rats: Quantitative assessment of tolerance and dependence. J. Pharmacol. Exp. Ther. 184, 404–408 (1973)
Gellert, V. F., Sparber, S. B.: A comparison of the effects of naloxone upon body weight loss and suppression of fixed-ratio operant behavior in morphine-dependent rats. J. Pharmacol. Exp. Ther. 201, 44–54 (1977)
Gibson, R. D., Tingstad, J. E.: Formulation of a morphine implantation pellet suitable for tolerance-physical dependence studies in mice. J. Pharm. Sci. 59, 426–427 (1970)
Herz, A., Teschemacher, H. J., Albus, K., Zieglgansberger, S.: Morphine abstinence syndrome in rabbits precipitated by injection of morphine antagonists into the ventricular system and restricted parts of it. Psychopharmacologia 26, 219–235 (1972)
Himmelsbach, C. K., Andrews, H. L.: Studies on modification of the morphine abstinence syndrome by drugs. J. Pharmacol. Exp. Ther. 77, 17–23 (1943)
Ho, I. K., Loh, H. H., Way, E. L.: Influence of 5,6-dihydroxytryptamine on morphine tolerance and physical dependence. Eur. J. Pharmacol. 21, 331–336 (1973)
Huidobro, F., Huidobro-Toro, J. P., Way, E. L.: Studies on tolerance development to single doses of morphine in mice. J. Pharmacol. Exp. Ther. 198, 318–329 (1976)
Hynes, M. D., Gianutsos, G., Lal, H.: Effects of cholinergic agonists and antagonists on morphine-withdrawal syndrome. Psychopharmacology 49, 191–195 (1976)
Jhamandas, K., Sutak, M., Bell, S.: Modification of precipitated morphine withdrawal syndrome by drugs affecting cholinergic mechanisms. Eur. J. Pharmacol. 24, 296–305 (1973)
Kaneto, H., Koida, M., Nakanishi, H.: Studies on physical dependence inducible by hours of exposure of mice to morphine. Jap. J. Pharmacol. 22, 755–766 (1972)
Kromer, W., Teschemacher, H.: An opiate withdrawal like phenomenon in the fetal guinea pig ileum upon naloxone challenge. Eur. J. Pharmacol. 49, 445–446 (1978)
Linseman, M. A.: Naloxone-precipitated withdrawal as a function of the morphine-naloxone interval. Pharmacology 54, 159–164 (1977)
Marshall, I., Weinstock, M.: A quantitative method for the assessment of physical dependence on narcotic analgesics in mice. Br. J. Pharmacol. 37, 505–506 P (1969)
Martin, W. R., Wikler, A., Eades, C. B., Pescor, R. T.: Tolerance to and physical dependence on morphine in rats. Psychopharmacologia (Berl.) 4, 249–260 (1962)
Menon, M. K., Tseng, L.-F., Loh, H. H., Clark, W. G.: An electromyographic method for the quantitative evaluation of narcotic analgesics in rats. Neuropharmacology 19, 231–236 (1980)
Meyer, D. R., Sparber, S. B.: A comparison of withdrawal in rats implanted with different types of morphine pellets. Pharmacol. Biochem. Behav. 5, 603–607 (1977)
Rodríguez, R., Luján, M., Campos, A. E., Chorné, R.: Morphine dependence in the isolated guinea pig ileum and its modification by p-chlorophenylalanine. Life Sci. 23, 913–920 (1978)
Schwartz, A. S., Eidelberg, E.: Role of biogenic amines in morphine dependence. Life Sci. 9, 613–624 (1970)
Smits, S. E.: Antagonism by naloxone of morphine-induced single-dose dependence and antinociception in mice. Res. Comm. Chem. Pharmacol. 15, 689–696 (1976)
Takemori, A. E., Sprague, G. L.: Comparison of naloxone-induced platform vertical jumping in the assessment of physical dependence in morphine-dependent mice. J. Pharm. Pharmacol. 30, 585–586 (1978)
Villarreal, J. E.: The effects of morphine agonists and antagonists on morphine-dependent rhesus monkeys. In: “Agonist and antagonist action of narcotic drugs” (H. W. Kosterlitz, H. O. J. Collier, J. E. Villarreal, eds.), pp. 73–93. Baltimore: University Park Press 1973
Watanabe, H.: The development of tolerance to and physical dependence on morphine following intraventricular injection in the rat. Jpn. J. Pharmacol. 21, 389–391 (1971)
Way, E. L., Loh, H. H., Shen, F.: Simultaneous quantitative assessment of morphine tolerance and physical dependence. J. Pharmacol. Exp. Ther. 167, 1–8 (1969)
Wei, E.: Morphine analgesia, tolerance and physical dependence in the adrenalectomized rat. Br. J. Pharmacol. 47, 693–699 (1973)
Wei, E., Loh, H. H., Way, E. L.: Quantitative aspects of precipitated abstinence in morphine-dependent rats. J. Pharmacol. Exp. Ther. 184, 398–403 (1973)
Yano, I., Takemori, A. E.: Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine. Res. Commun. Chem. Pathol. Pharmacol. 16, 721–734 (1977)
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Deceased February 13, 1979
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Menon, M.K., Tseng, LF., Loh, H.H. et al. An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 312, 43–49 (1980). https://doi.org/10.1007/BF00502573
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DOI: https://doi.org/10.1007/BF00502573